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01.
medRxiv (Medicine) 2026-06-17

Efficacy of a Gamified Digital Platform for Substance Use Education and Overdose Prevention Among College Students: a Pilot and Feasibility Study

Background: For US young adults aged 18-25 in the 2018-2024 period, fentanyl was involved in 78.2% of the 44,020 unintentional or undetermined-intent overdose deaths, most often co-involving stimulants and other non-opioid substances. While fatal overdose rates in this age group have fallen to their lowest recorded level, emergency medical services-attended non-fatal overdose events have reached record highs, shifting the decisive variable toward bystander recognition and response. College students report near-universal alcohol education but minimal education on the substances actually driving overdose mortality. Methods: We conducted a single-group pre-post evaluation of the DopaGE Portal, a gamified, mastery-based digital platform covering cocaine, MDMA, benzodiazepines, and opioid overdose response, deployed at a public university (UNL) and a multi-campus volunteer network (TACO). Paired pre/post surveys (N=42) measured self-efficacy (7 items; primary), behavioral intentions, risk perception, and knowledge/attitudes on 5-point scales, plus four factual knowledge questions. Paired t-tests, exact McNemar tests, and Benjamini-Hochberg correction across eight primary tests were applied. Institutional naloxone distribution at UNL was tracked as an ecological behavioral outcome. A mandated high-school cohort (N=94) provided supplementary acceptability data. Results: Self-efficacy increased from 2.82 to 4.46 (d=2.00, 95% CI 1.46-2.55; adjusted p

02.
medRxiv (Medicine) 2026-06-23

Novel loci and multi-omics risk models for rheumatoid arthritis through a million-participant genome-wide association meta-analysis

Rheumatoid arthritis (RA) remains incompletely understood, limiting targeted prevention. In this work, genome-wide association study meta-analyses were performed for RA and seropositive RA, comprising approximately one million participants of European ancestry. Eight and six novel genomic risk loci were defined for RA and seropositive RA, and candidate causal genes were identified, highlighting relevant biological pathways, including established immune pathways and estrogen metabolism. Novel disease-specific polygenic risk scores (PRSs) were constructed, enhancing predictive performance over clinical risk factors (incremental C-statistics of 2.7 and 5.1 for RA and seropositive RA, respectively). In parallel, integrating metabolomic data into high-dimensional models enhanced risk stratification over models based on clinical risk factors and genomics, particularly for seropositive RA, where the hazard ratio of the highest decile increased from 4.869 to 5.697. These findings expand the understanding of genetic factors underlying RA and support the value of including PRSs in risk assessment, while suggesting metabolomic integration may further enhance risk stratification, particularly for seropositive RA.

03.
medRxiv (Medicine) 2026-06-18

Chest X-Ray as a critical screening tool for Household Contacts of TB: Lessons from Three Years of Programmatic Data in India

Introduction: Household contacts (HHCs) of pulmonary TB patients remain at high risk for TB infection and disease progression, yet many remain asymptomatic and are missed by symptom-screening pathways. While India expanded its TB preventative guidelines to include all HHCs in 2021, chest X-ray (CXR) screening continues to be used selectively, representing a missed opportunity in early case detection. Methods: The analysis uses programmatic data from Project JEET 2.0 (Joint Effort for Elimination of Tuberculosis), implemented by the William J. Clinton Foundation in India, between October 2021 and March 2024. Eligible HHCs (>=5 years) were offered CXR screening as part of TB preventive therapy (TPT) evaluation. Descriptive and multivariable analyses examined predictors of CXR uptake and TB yield. A two-stage logistic regression model estimated potential TB yield under universal CXR coverage. Model performance was evaluated using the area under the curve (AUC), and bootstrap simulations generated counterfactual estimates of missed TB cases. Results: Among 1,034,621 HHCs, 1.02% individuals were found positive for TB, which includes 7,786 HHCs who were on TB treatment already, while an additional 2,812 were identified during pre-TPT evaluation. Among eligible HHCs (n = 1,026,835), 70% were screened with CXR, of which 2.4% had suggestive TB findings. Of these, 79% went for further TB assessment. Symptomatic HHCs were more likely to be CXR screened (84% vs 69%) and assessed for TB, yet two-thirds of all detected TB cases were asymptomatic. It is estimated that universal CXR coverage and TB testing for suggestive cases can increase TB detection by at least 87%. Conclusion: The study provides a scalable approach to expand CXR coverage through public-private partnerships, enabling early TB detection among HHCs, especially among asymptomatic contacts. Future implementations will benefit from integrating AI-enabled reading, along with systematic follow up for those with suggestive findings.

04.
arXiv (quant-ph) 2026-06-15

Landscape-Similarity-Guided Optimization in Divide-and-Conquer QAOA

arXiv:2602.21689v3 Announce Type: replace Abstract: Divide-and-conquer strategies mitigate hardware constraints for the Quantum Approximate Optimization Algorithm (QAOA) on Noisy Intermediate-Scale Quantum (NISQ) devices by partitioning large interaction graphs into smaller, hardware-compatible sub-problems. However, this approach introduces a severe classical training bottleneck: a decomposition across $m$ boundary nodes generates $2^m$ distinct sub-problems that typically require independent optimization. In this work, we demonstrate that across diverse synthetic and real-world interaction graphs, the variational landscapes of these reduced QAOA instances actually exhibit a robust universality. Adapting the replica-overlap framework of spin-glass physics, we define a landscape-overlap order parameter $q$ to quantify geometric correlations between energy landscapes, revealing a sharp landscape-similarity transition as graph connectivity is tuned. Exploiting this, we introduce Doubly Optimized QAOA (DO-QAOA), an adaptive pipeline that collapses the sub-problems from $2^m$ distinct sub-problems into $K=\mathcal{O}(1)$ effective landscape classes. By performing optimization on a single representative sub-problem and dynamically transferring parameters to remaining sub-problems, DO-QAOA lowers runtime and quantum measurement overhead by orders of magnitude while maintaining a competitive Approximation Ratio Gap (ARG).

05.
arXiv (CS.LG) 2026-06-15

Direct Fisher Score Estimation for Likelihood Maximization

arXiv:2506.06542v2 Announce Type: replace-cross Abstract: We study the problem of likelihood maximization when the likelihood function is intractable but model simulations are readily available. We propose a sequential, gradient-based optimization method that directly models the Fisher score based on a local score matching technique which uses simulations from a localized region around each parameter iterate. By employing a linear parameterization to the surrogate score model, our technique admits a closed-form, least-squares solution. This approach yields a fast, flexible, and efficient approximation to the Fisher score, effectively smoothing the likelihood objective and mitigating the challenges posed by complex likelihood landscapes. We provide theoretical guarantees for our score estimator, including bounds on the bias introduced by the smoothing. Empirical results on a range of synthetic and real-world problems demonstrate the superior performance of our method compared to existing benchmarks.

06.
arXiv (CS.AI) 2026-06-24

TACTFUL: Tactile-Driven Exploration For Object Localization and Identification in Confined Environments

arXiv:2606.24712v1 Announce Type: cross Abstract: Humans effortlessly locate and identify objects by touch alone, even without vision. In contrast, robotic systems rely heavily on vision and struggle with autonomous tactile exploration and object identification. We present TACTFUL, a vision-free tactile exploration framework that enables a multi-fingered robot to autonomously explore confined workspaces, discover objects through contact, and identify them via tactile reconstruction. Trained entirely on real hardware without simulation, our system learns a single policy that balances global workspace exploration with local surface refinement through a dynamic reward schedule. Our results demonstrate that tactile sensing, when paired with structured learning, can serve as an effective primary modality for object-level reasoning, achieving 77% success with 0.015 m average reconstruction error and outperforming baseline approaches on real-world objects.

07.
arXiv (CS.CV) 2026-06-24

UniTranslator: A Unified Multi-modal Framework for End-to-end In-Image Machine Translation

In-Image Machine Translation (IIMT) aims to translate scene text in an image and render the translated text back into the original regions while preserving the overall visual appearance. Recent unified multimodal models provide a promising solution by combining visual-text understanding and image generation within a single framework. However, directly adapting such models to IIMT remains challenging. In particular, they often suffer from understanding-generation conflicts, where the translation inferred during understanding is inconsistent with the text supervision used in generation, and spatial position misalignment, where the rendered text does not accurately match the target text regions. To address these issues, we present UniTranslator, a unified multimodal framework for IIMT that tightly couples translation understanding and text editing. Specifically, we introduce an Understand-Generation Alignment Module (UGAM) to bridge the representation gap between understanding and generation, encouraging semantic consistency between translated content prediction and text rendering. We further propose a Spatial Mask Decoder (SMD) with pixel-level supervision over text regions to improve spatial grounding, geometric alignment, and layout controllability during generation. Extensive experiments on multiple benchmarks demonstrate that UniTranslator achieves state-of-the-art performance across diverse language directions and complex real-world layouts. Moreover, our results reveal a strong mutual reinforcement effect between translation understanding and image generation, highlighting the advantage of unified translation multimodal learning. Code is available at https://github.com/SeerRay-Lab/Unitranslator.

08.
arXiv (quant-ph) 2026-06-25

Neural network decoder confidence as a learned proxy for the logical gap

arXiv:2606.08758v2 Announce Type: replace Abstract: To utilize quantum error-correcting codes, a decoder must infer the logical sector from the measured syndrome. Beyond producing a hard logical decision, some decoders provide soft information that estimates the reliability of that decision. For minimum-weight perfect matching (MWPM), a common confidence measure is the complementary, or logical, gap. Here we test whether the logit of a graph neural network (GNN) decoder can act as a learned proxy for the logical gap. Using a pretrained GNN for the rotated surface code under uniform circuit-level noise [Physical Review Research, 7(2):023181, 2025], we compare its soft output with the MWPM complementary gap on the same sampled syndromes. We find that post-selection based on the GNN logit yields a lower logical error rate than one based on the MWPM gap. Shot-by-shot, the signed GNN confidence distribution resembles the signed MWPM gap at low and intermediate values, but assigns higher confidence to many correctly decoded shots. While both scores approximate the posterior log-likelihood ratio, the GNN confidence magnitude is closer to its ideal value. These results show that a neural-network decoder trained only on syndromes and logical labels learns both gap-like discrimination and a quantitative confidence scale, enabling confidence-based post-selection when MWPM gap estimates are unavailable, costly, or poorly matched to the noise model.

09.
arXiv (CS.AI) 2026-06-25

ZeroWBC: Learning Natural Whole-Body Humanoid Interaction from Human Egocentric Data

arXiv:2603.09170v3 Announce Type: replace-cross Abstract: Achieving versatile and natural whole-body humanoid interaction control remains challenging due to the high cost of whole-body teleoperation data. We present ZeroWBC, a teleoperation-free framework that learns humanoid whole-body interaction from human egocentric videos paired with synchronized whole-body motion and text annotations. ZeroWBC adopts a generation-then-tracking formulation to tackle the static scene whole-body interaction control problem. Given an initial egocentric image and a language instruction, a fine-tuned Vision-Language Model generates future human whole-body motion tokens, which are decoded into continuous motions and retargeted to the humanoid. The resulting reference motions, together with root and key body-part trajectories, are then executed by a general interactive motion tracking policy. To improve interaction performance, we introduce an interaction-oriented tracking reward that prioritizes global root and key body-part trajectory alignment while preserving natural whole-body motion. Experiments on the Unitree G1 humanoid robot show that ZeroWBC enables diverse scene-aware behaviors without robot teleoperation demonstrations. These results suggest a scalable paradigm for learning natural humanoid whole-body interaction from human egocentric data.

10.
arXiv (CS.CV) 2026-06-12

SeamEdit: A Black-Box VLM-Agnostic Pipeline for Large-Image Semantic Editing

Semantic region editing for large images must satisfy two requirements at the same time: high generative quality and natural integration with surrounding content. Some related methods rely on white-box models and leave the strong generation capability of closed-source models underexplored. Directly applying closed-source models to tiled editing, however, introduces several failure modes: semantic deformation, canvas-level alignment drift, and visible seam artifacts. This paper presents SeamEdit, a training-free and model-agnostic pipeline that treats any VLM with inpainting capability as a black-box oracle. SeamEdit mitigates these issues through a five-stage post-hoc pipeline: overlay-based tile decomposition, black-box VLM inpainting, geometric and color-consistency correction, seam-risk-based multi-candidate ranking, and dynamic-programming curved seam fusion. The pipeline reduces seam visibility and supports semantic modification of arbitrary tile regions.

11.
arXiv (quant-ph) 2026-06-16

Synthesizing Arbitrary Non-Hermitian Hamiltonian with Stochastic Floquet Engineering

arXiv:2606.15664v1 Announce Type: new Abstract: The conventional Floquet engineering scheme synthesizes a given target Hamiltonian with a deterministic temporal periodic driving field. In this work, we introduce the stochastic Floquet engineering scheme that can synthesize an arbitrary non-Hermitian target Hamiltonian using a time-periodic driving field with noisy amplitude. Our method is rooted in the Hermitian dynamics taking noise as a valuable quantum resource with no need for loss or gain in prior. We apply our method to engineer a cavity Hamiltonian with dissipative coupling between Fock states, and to prepare a given quantum state from a generally arbitrary quantum state. The stochastic Floqut engineering also provides a way to generate non-unitary quantum gates, which take advantage in certain tasks compared to unitary quantum computing, without the need for ancillae or state-dependent updating.

12.
arXiv (CS.CV) 2026-06-17

Robustness of Similarity-based Positional Encoding Under Rotations: Theoretical Analysis and Experimental Validation

Positional encoding is a fundamental component of Transformer architectures, as it injects information about the spatial or sequential arrangement of inputs. Among recent alternatives to standard absolute and sinusoidal encodings, similarity-based positional encoding (simPE) has emerged as a flexible framework for representing positional structure through pairwise relations. simPE was originally designed for medical imaging applications, where geometric robustness is especially relevant: small rotations naturally arise during image acquisition, induced by imaging instruments, patient positioning, or slight acquisition misalignments. Despite its empirical promise, the theoretical behavior of simPE under geometric perturbations has not been fully characterized. In this paper, we study the robustness of simPE with respect to rotations, combining formal theoretical analysis with experimental validation. We first show that simPE is generally not rotation-invariant. We then prove that, under mild Lipschitz assumptions on the elementary components, simPE is stable under rotational perturbations and derive explicit perturbation bounds in Frobenius norm. We validate these findings experimentally on four controlled datasets–a synthetic Arrow dataset, a synthetic Shapes dataset (four geometric shape categories), a synthetic Digits dataset, and a benchmark image classification dataset (FashionMNIST)–in which training and validation images are kept in a fixed canonical orientation while test images are subjected to increasing rotation angles. Across all datasets, simPE consistently outperforms standard learned positional encoding in terms of accuracy, F1 score, precision, and recall under rotation, particularly in the small-to-moderate angle regime, corroborating the theoretical stability guarantees.

13.
arXiv (CS.CV) 2026-06-19

Collaborative Multi-Modal Coding for High-Quality 3D Generation

3D content inherently encompasses multi-modal characteristics and can be projected into different modalities (e.g., RGB images, RGBD, and point clouds). Each modality exhibits distinct advantages in 3D asset modeling: RGB images contain vivid 3D textures, whereas point clouds define fine-grained 3D geometries. However, most existing 3D-native generative architectures either operate predominantly within single-modality paradigms-thus overlooking the complementary benefits of multi-modality data-or restrict themselves to 3D structures, thereby limiting the scope of available training datasets. To holistically harness multi-modalities for 3D modeling, we present TriMM, the first feed-forward 3D-native generative model that learns from basic multi-modalities (e.g., RGB, RGBD, and point cloud). Specifically, 1) TriMM first introduces collaborative multi-modal coding, which integrates modality-specific features while preserving their unique representational strengths. 2) Furthermore, auxiliary 2D and 3D supervision are introduced to raise the robustness and performance of multi-modal coding. 3) Based on the embedded multi-modal code, TriMM employs a triplane latent diffusion model to generate 3D assets of superior quality, enhancing both the texture and the geometric detail. Extensive experiments on multiple well-known datasets demonstrate that TriMM, by effectively leveraging multi-modality, achieves competitive performance with models trained on large-scale datasets, despite utilizing a small amount of training data. Furthermore, we conduct additional experiments on recent RGB-D datasets, verifying the feasibility of incorporating other multi-modal datasets into 3D generation.

14.
arXiv (CS.CV) 2026-06-25

SeFi-Image: A Text-to-Image Foundation Model with Semantic-First Diffusion

作者:

Training image generation foundation models consumes substantial resources. Previous methods have attempted to leverage semantic guidance to accelerate the training process, yet their experiments were only conducted on simple datasets such as ImageNet, at low resolutions, and with small-scale models. In this paper, we propose SeFi-Image, a text-to-image foundation model built upon semantic-first diffusion, a novel latent diffusion modeling paradigm. We instantiate SeFi-Image at three model scales, 1B, 2B, and 5B parameters, enabling systematic study of scaling behavior and flexible deployment under varying compute budgets. Notably, our largest 5B model was trained with merely 125K A800 GPU hours, corresponding to roughly 10-20% of the training compute used by Z-Image. However, it achieves results comparable to or even superior to Qwen-Image and Z-Image. Despite this modest training compute, SeFi-Image achieves strong performance on a wide range of benchmarks, including GenEval, DPG, LongTextBench, OneIG, and CVTG-2K. Moreover, we provide DMD2-distilled few-step turbo variants for each model scale to accommodate diverse hardware constraints and latency requirements. We publicly release our code, weights and hope this work offers the community useful insights into semantic-guided diffusion modeling for T2I generation, while also providing practical and readily deployable model options.

15.
medRxiv (Medicine) 2026-06-23

Systemic and Mucosal Antibody Correlates of Protection Against Bordetella pertussis in a Controlled Human Infection Model

Abstract Background Despite high vaccination coverage, pertussis has resurged globally. Whole-cell (wP) and acellular (aP) pertussis vaccines induce distinct immune profiles, yet immune correlates of protection against infection and symptomatic disease remain incompletely defined. We leveraged a controlled human infection model (CHIM) to identify systemic and mucosal humoral signatures associated with resistance to Bordetella pertussis. Methods Adults with documented history of vaccination had previously been enrolled in a CHIM study and challenged intranasally with B. pertussis D420. For the present work, longitudinal serum and nasal wash samples were analyzed using systems serology to comprehensively profile antibody features. Multivariate modeling and network analyses were performed to define discriminatory immune features. Findings Baseline aP vaccine antigen-specific antibodies did not distinguish infection outcomes. In wP-primed individuals, protection from B. pertussis infection was associated with broad, high-magnitude, polyfunctional antibody responses targeting non-canonical antigens, including BrkA, TcfA, OmpP, OmlA, FauA, and Pal. Protective signatures associated with resistance to symptomatic disease in both vaccine groups were characterized by enhanced Fc-receptor-engaging antibody profiles with distinct antigenic patterns shaped by vaccine history. Importantly, while conventional aP vaccine antigens failed to reliably distinguish individuals susceptible to infection or symptom development, correlates generated by integrated serum and mucosal models based on select non-canonical antigens achieved near-perfect discrimination of infection and symptom outcomes, outperforming models restricted to aP-vaccine. antigens only. Interpretation Resistance to infection was largely restricted to wP-primed individuals and was associated with integrated systemic and mucosal antibody responses directed against antigens beyond those included in acellular vaccines. Protection from symptomatic disease in both vaccine groups was linked to distinct antibody response signatures, shaped by prior vaccination history. These findings indicate that immune mechanisms preventing infection differ from those limiting clinical disease and provide a framework for redesign of next-generation pertussis vaccines aimed at blocking infection and symptomatic disease.

16.
arXiv (CS.AI) 2026-06-19

Speeding up the annotation process in semantic segmentation industrial applications

arXiv:2606.19934v1 Announce Type: cross Abstract: Current machine learning models commonly require large and well-annotated datasets. However, the annotation process often becomes a bottleneck, with increased complexity leading to higher chances of human errors. Within this context, our goal in this paper is to leverage unsupervised algorithms to improve data annotation efficiency for complex semantic segmentation problems in industrial materials science. Previous research has quantified labeling time and others explored unsupervised methods. However, to the best of our knowledge, this is the first study to quantify how much unsupervised algorithms accelerate the labeling process. We aim to validate the extent to which this laborious process can be accelerated, focusing on semantic segmentation tasks that involve annotating each pixel of high-resolution images, such as the microstructure characterization challenge in materials science. Specifically, we demonstrate that by using unsupervised computer vision algorithms, the time required for the labeling process can be reduced from 170 hours to 37 hours, achieving an approximate reduction of 78\%. The dataset we work with includes large images of dimensions 1280x959 and 960x703, which further increases the complexity of the annotation task. Despite these challenges, we create and share the largest public steel microstructure segmentation dataset to date, available under MIT License with permanent DOI, contributing a fully annotated, high-resolution dataset to the field. Additionally, this is the first work to compare the labeling time from scratch (a common approach in previous studies) to the labeling time when using these unsupervised algorithms as a pre-annotation step. Furthermore, we provide a Deep Learning model trained on this dataset, validated by field experts, and deployed in an industrial setting, serving as an initial benchmark for this public dataset.

17.
arXiv (CS.CV) 2026-06-16

SGFormer++: Semantic Graph Transformer for Incremental 3D Scene Graph Generation

In this paper, we propose SGFormer++, a novel Semantic Graph Transformer for 3D scene graph generation (SGG), which aims to parse point cloud scenes into semantic structural graphs, where nodes denote detected object instances and edges encode their pairwise relationships, with the core challenge lying in modeling complex global scene structure. While existing graph convolutional network (GCN)-based methods suffer from over-smoothing and limited receptive fields, SGFormer++ leverages Transformer layers as its backbone to enable global message passing. Specifically, we introduce two key components tailored for 3D SGG: (1) a Graph Embedding Layer++ that efficiently integrates edge-aware global context with linear computational complexity, and (2) a Semantic Injection Layer++ that enriches visual features with linguistic priors from large language models (LLMs) and vision-language models (VLMs), boosting semantic representation without introducing extra trainable parameters. To further address the practical challenge of incremental SGG (I-SGG), where new relationship categories arrive sequentially, we equip SGFormer++ with a novel Spatial-guided Feature Adapter, which calibrates predicate features using subject-object spatial geometry to counter scale variation, and a Cascaded Binary Prediction Head that mitigates catastrophic forgetting via task-incremental classifier expansion and logit distillation. Extensive experiments on the 3DSSG benchmark demonstrate that SGFormer++ achieves state-of-the-art performance in both standard and incremental settings: it yields a significant 4.49% absolute improvement in Predicate A@1 under the incremental setting. Code and data are available at: https://github.com/Andy20178/SGFormer.

18.
arXiv (CS.LG) 2026-06-25

Do Prompt-Elicited Trajectories Reflect Training-Time Reward Hacking? A Systematic Study on Monitoring Trainig-Time Reward Hacking in Code Generation

arXiv:2604.23488v2 Announce Type: replace Abstract: Reward hacking in code generation, where models exploit evaluation loopholes to obtain high reward without correctly solving the intended task, poses a critical challenge for Reinforcement Learning (RL) and the deployment of reasoning models. Existing studies often rely on explicitly prompted hacking trajectories, but it remains unclear whether monitors trained on such data can detect reward hacks that arise without direct hacking instructions during RL training. In this work, we introduce Trace-and-Amplify, a framework for scalable curation of reward-hacking trajectories that arise during RL training without explicit hacking instructions. The framework uses unit-test tracers to identify hacking solutions when they occur and retains such trajectories for monitor training and evaluation. Through controlled comparisons between monitors trained on prompt-elicited hacking trajectories and training-time reward-hacking trajectories collected by Trace-and-Amplify, we find that (1) prompt-elicited-data-trained monitors often fail to generalize to trajectories curated by our framework, and (2) monitors trained on our Trace-and-Amplify trajectories demonstrate stronger generalizability to unseen hacking types. Our results indicate that prompted reward hacking data may not fully reflect training-time reward-hacking behaviors, and that relying solely on these data can lead to misleading conclusions. Codebase is available at https://github.com/LichenLillc/CoTMonitoring.git

19.
PLOS Computational Biology 2026-06-17

Machine learning-driven identification of virulence determinants in <i>Borrelia burgdorferi</i> associated with human dissemination

by Hoa Thanh Nguyen, Catherine A. Brissette Lyme disease, the most common tick-borne infectious disease in the United States, presents with highly variable clinical outcomes, ranging from localized erythema migrans to severe disseminated complications affecting the heart, joints, and nervous system. The bacterial determinants underlying this phenotypic variation remain largely unknown, limiting our ability to predict disease progression and optimize treatment strategies. Here, we applied machine learning (ML) approaches to identify specific amino acid residues within surface-exposed virulence factors that predict human dissemination phenotypes. Utilizing the published whole genome sequences from 299 clinical Borrelia burgdorferi isolates collected from the United States and Slovenia over a 30-year period (1992–2021), we extracted and characterized translated amino acid sequences (variants) of seven known virulence factors (BB_0406, BBK32, DbpA, OspA, OspC, P66, and RevA). Protein variants were classified based on their association with disseminated versus localized infections using clinical metadata. Cramér’s V analysis revealed possible strong associations between dissemination phenotypes and five adhesins: BBK32, DbpA, OspC, P66, and RevA. We developed ML models using five algorithms with multiple feature selection strategies, achieving robust predictive performance for DbpA, OspC, and RevA variants (all performance metrics > 0.7). Feature importance analysis identified 57, 29, and 42 key predictive residues for DbpA, OspC, and RevA, respectively. Notably, B-cell epitope prediction revealed significant enrichment of ML-identified residues within predicted epitope regions for OspC (11 overlapping residues, OR = 3.57, p = 0.006) and RevA (12 overlapping residues, OR = 2.37, p = 0.048), suggesting these residues may influence immune recognition and bacterial persistence. This study establishes the first computational framework linking Borrelia protein sequence variants to clinical dissemination phenotypes, providing molecular insights into Lyme disease pathogenesis that may inform the development of improved diagnostics and therapeutic targets.

20.
medRxiv (Medicine) 2026-06-24

Predicting 24-Month MCI-to-Alzheimer's Conversion Using Routine Clinical Assessments Without Neuroimaging or Genetic Testing

作者:

ABSTRACT INTRODUCTION: Early identification of individuals with mild cognitive impairment (MCI) at high risk of conversion to Alzheimer's disease (AD) is essential for timely intervention. We evaluated whether routinely obtainable clinical assessments can accurately predict 24-month MC to AD conversion. METHODS: Data from 2,430 participants with MCI in the Alzheimer's Disease Neuroimaging Initiative were analyzed. XGBoost, Random Forest, and Logistic Regression models were evaluated. SHAP-based feature selection and feature ablation analyses assessed the incremental value of APOE4 genotype. RESULTS: A six-feature model incorporating age, sex, education, RAVLT Immediate Recall, MMSE, and EcogSPTotal achieved an AUC of 0.922 (95% CI, 0.911~0.933). APOE4 provided negligible additional predictive value once cognitive measures were included. The XGBoost model outperformed Clinical Dementia Rating Sum of Boxes classification. DISCUSSION: Routine cognitive assessments accurately predict 24-month MCI-to-AD progression without biomarkers, neuroimaging, or genetic testing, offering a practical, low-cost tool for clinical risk stratification.

21.
arXiv (CS.LG) 2026-06-19

Meta Flow Maps enable scalable reward alignment

arXiv:2601.14430v2 Announce Type: replace-cross Abstract: Controlling generative models is computationally expensive. This is because optimal alignment with a reward function–whether via inference-time steering or fine-tuning–requires estimating the value function. This task demands access to the conditional posterior $p_{1|t}(x_1|x_t)$, the distribution of clean data $x_1$ consistent with an intermediate state $x_t$, a requirement that typically compels methods to resort to costly trajectory simulations. To address this bottleneck, we introduce Meta Flow Maps (MFMs), a framework extending consistency models and flow maps into the stochastic regime. MFMs are trained to perform stochastic one-step posterior sampling, generating arbitrarily many i.i.d. draws of clean data $x_1$ from any intermediate state. Crucially, these samples provide a differentiable reparametrization that unlocks efficient value function estimation. We leverage this capability to solve bottlenecks in both paradigms: enabling inference-time steering without inner rollouts, and facilitating unbiased, off-policy fine-tuning to general rewards. Empirically, our single-particle steered-MFM sampler outperforms a Best-of-1000 baseline on ImageNet across multiple rewards at a fraction of the compute.

22.
medRxiv (Medicine) 2026-06-17

Characterisation of disease progression in hantavirus haemorrhagic fever with renal syndrome

Hantaviruses can cause haemorrhagic fever with renal syndrome (HFRS). This is a clinically variable disease in which severe outcomes are hypothesized to arise from dysregulated host responses. To characterise this, longitudinal, label-free plasma proteomics was used to compare disease progression in a unique well-defined cohort of patients infected with either Dobrava virus (DOBV) or Puumala virus (PUUV) hantaviruses. Patients were stratified by clinical severity. The average viral load in the first available sample from hospitalized patients was higher in those who went on to have severe infection, and higher in patients infected with DOBV. There was marked separation of infected patients from controls across early, mid and late disease, including after viral RNA clearance, suggesting a sustained systemic host-response signature. Proteomic signatures were consistent with a strong acute-phase response in both mild and severe disease. There was evidence of activation of the adaptive humoral response at later stages. Hierarchical clustering identified severity-associated pathways linked to endothelial dysfunction, thrombocytopenia, vascular leakage and renal injury. These findings define a durable plasma proteomic signature of hantavirus disease and support a model in which severe HFRS is driven by persistent inflammatory, complement and platelet/coagulation pathway activation rather than viral burden alone.

23.
arXiv (CS.AI) 2026-06-19

The Hidden Evolution of Disguised Visual Context inside the VLM

arXiv:2606.20077v1 Announce Type: cross Abstract: Visual tokens enter Large Language Models (LLMs) as raw, foreign signals. How they are transformed into meaningful representations and interact with the language space depends entirely on the integration architecture. Whether by treating visual tokens as in-context prompts within the input sequence or injecting them directly into the LLM's intermediate layers. A controlled comparison and understanding of how these architectural choices affect visual information and its internal transformation to integrate with the LLM remains underexplored. We provide a fair comparison by evaluating in-context and layer-wise injection VLM integration paradigms under identical training conditions across single image, multi-image, and video benchmarks. In doing so, we uncover a hidden evolution where visual tokens enter the LLM as disguised visual context, raw representations lacking linguistic structure, but are progressively reshaped depending on the integration paradigm, each capturing fundamentally different frequency characteristics of the visual signal. We show that this evolution inside the LLM determines what visual features the VLM can utilize effectively, how visual representations align with the language space, and ultimately how each paradigm performs across different tasks. We further demonstrate that attention allocation alone is insufficient, and that performance is driven by the quality of visual representations at each layer.

24.
arXiv (CS.LG) 2026-06-12

Quantum Reservoir Computing for Short-Term Power Load Forecasting in Resource-Constrained Energy Systems

arXiv:2606.12806v1 Announce Type: cross Abstract: Short-term load forecasting is essential for reliable energy management, but practical deployment on edge devices requires models that remain accurate under limited memory, finite measurement budgets, and hardware noise. This work proposes a hardware-efficient Quantum Reservoir Computing (QRC) framework for energy load forecasting, where a fixed quantum reservoir transforms temporal input windows into high-dimensional features and only a classical Elastic Net readout is trained. To reduce deployment cost, the trained readout is compressed using post-training fixed-point quantization at bit widths from 8 to 2 bits. The framework is evaluated on the Tetouan and Spain energy load datasets under exact statevector simulation, 512-shot finite sampling, and realistic hardware-noise models from IBM FakeTorino and IBM FakeMarrakesh. Results show that 6-bit readout precision preserves full-precision forecasting performance while reducing readout memory by 81.2%. Below this point, degradation becomes dataset dependent, with Tetouan showing stronger sensitivity and Spain degrading more gradually. Hardware-noise validation further shows that the trained readout transfers to noisy reservoir states without retraining. These findings support quantized QRC as a resource-aware forecasting approach for near-term quantum time-series applications.

25.
bioRxiv (Bioinfo) 2026-06-24

fastQpick: scalable bootstrap and subsampling of FASTQ reads

fastQpick is a command-line tool and Python library for sampling FASTQ reads with replacement. Sampling with replacement turns a single FASTQ file into an arbitrary number of bootstrap replicates, which enables uncertainty quantification and statistical analysis at the level of raw reads. This process answers questions such as how much an abundance estimate would change if the library were resequenced, or whether a low-abundance call is robust to the particular reads that were sequenced. fastQpick works efficiently on large libraries by streaming files in two passes by default: first to count reads and create a hash-based counter, and then to write the sample. It generates a full-size bootstrap replicate of a 500-million-read library in under 30 minutes with 9.4 GB of peak memory, with a low-memory mode that reduces the peak to 1.4 GB. A single-pass mode draws samples in a single read through the file, using O(1) working memory and producing an output size that is exact in expectation but not fixed. In a real yeast RNA-seq experiment, bootstrap replicates generated by fastQpick recover the sampling uncertainty of transcript abundance estimates, matching the analytic multinomial standard errors to within a few percent. fastQpick is open source and freely available under the MIT license on GitHub at https://github.com/pachterlab/fastQpick and on PyPI (pip install fastQpick).